Numerous reports have documented a markedly increased incidence of disordered mineral metabolism and bone changes of osteomalacia in patients on chronic anticonvulsant drug therapy. Recent studies from our laboratory have demonstrated (1) a significant incidence of hypocalcemia, reduced serum 25-hydroxycalciferol levels and osteopenia in patients on chronic anticonvulsant therapy and (2) definite drug-induced alterations in the in vivo and in vitro metabolism of vitamin D. The purposes of the proposed investigations will be (1) to employ the most sensitive available techniques, including serum vitamin D metabolite assays and photon absorption measurements of bone mineral content, to determine the incidence of and predisposing risk factors in the development of clinical evidence of disordered mineral metabolism in outpatients and institutionalized patients receiving chronic anticonvulsant or psychoactive drug therapy, (2) to quantitate the effects of treatment with these agents on the metabolism and biologic activity of vitamin D, 250HD and 1,25(OH)2D in reversing drug-induced biochemical and histologic abnormalities, and (4) to explore through in vivo and in vitro animal studies the mechanisms whereby anticonvulsant drug administration alters the metabolism of mineral, vitamin D and bone. Specific areas to be investigated during the coming year include: the effects of anticonvulsant drugs and steroid hormones on parathyroid hormone, vitamin D, mineral and bone metabolism in man; mechanisms of anticonvulsant drug effects on intestine, bone, muscle and renal calcium and phosphate transport in animals in vivo, and the direct effect of anticonvulsant drugs on bone and bone cell metabolism in vitro. BIBLIOGRAPHIC REFERENCES: Hahn, T.J., Scharp, C.R., Halstead, L.R., Haddad, J.G., Karl, D.M. and Avioli, L.V.: Parathyroid Hormone Status and Renal Responsiveness in Familial Hypophosphatemic Rickets. J. Clin. Endocr. and Metab. 41: 926, 1975. Hahn, T.J.: Bone Complications of Anticonvulsants. Drugs 12: 161, 1976.